Clinical Observation Of Combined Regional Hyperthermia And Chemotherapy On Immunity Of Pancreatic Cancer

Background: Pancreatic cancer is one of the most common malignant tumors of digestive tract.For its special anatomical location and biological characteristics,most of the pancreatic lesions are difficult to detect in the early stage,and the clinical symptoms are atypical.Most patients are diagnosed in the middle and late stages.The incidence of pancreatic cancer is increasing year by year.Comprehensive treatment is mostly used for pancreatic cancer patients,but the overall benefit is not satisfactory.This study has combined regional hyperthermia with chemotherapy to explore its efficiency and effect on immunity of pancreatic cancer.Objective: Clinical data of pancreatic cancer patients treated with combined regional hyperthermia and chemotherapy or chemotherapy alone were collected to compare the efficiency and immune status of patients.This study also explored the prognostic value of immunity related indicators in peripheral blood to confirm that combined regional hyperthermia and chemotherapy is efficient in the treatment of pancreatic cancer to further improve overall survival.Method: A total of 61 patients with pancreatic cancer treated by either combined regional hyperthermia and chemotherapy or chemotherapy alone were collected in the Department of Oncology,the Second Affiliated Hospital of Dalian Medical University between 2014.01 and 2018.08.Their clinical data were collected for analysis,including age,sex,stage,tumor location,metastasis status,treatment regimens,disease-free survival(DFS)after surgery,objective remission rate(ORR),disease control rate(DCR),and progression-free survival(PFS)of advanced patients,overall survival(OS),and immune indicators which consist of lymphocyte subsets,white blood cells,neutrophils,lymphocytes,platelets,systemic immune-inflammatory index(SII =platelet number × neutrophil number / lymphocyte),neutrophil to lymphocyte ratio(NLR),and platelet to lymphocyte ratio(PLR).Follow-up was carried out by telephone and visiting to the hospital,which was up to 2019.01.01.Kaplan-Meier method wasused for survival analysis,Log-rank test was used for inter-group comparison,and Cox regression model was used for multivariate analysis of combined effects on survival and prognosis.Result: 1.In the first-line treatment of advanced patients,ORR and DCR of the thermochemotherapy group were higher than those of chemotherapy group without statistical significance.2.Among 61 pancreatic cancer patients,mOS of thermochemotherapy group and chemotherapy group were 21 m vs18m,(P>0.05)..In subset of 19 adjuvant therapy,The mDFS and mOS of thermochemotherapy group were 16 m and 39 m,higher than11 m and 24 m in chemotherapy group,but there was no statistical significanc(P>0.05).In subset of 42 first-line therapy,mPFS of thermochemotherapy and chemotherapy group were 10 m vs 6m with significantly statistical different(P=0.009).mOS were 17 m vs 15m(P>0.05).3.The incidence of bone marrow suppression and gastrointestinal reactions in thermochemotherapy group was slightly higher than those in the chemotherapy group,while the incidence of liver dysfunction and skin rash in the combined therapy group was slightly lower than that the chemotherapy group.4.Lymphocyte subsets analysis showed that compared with chemotherapy group,CD4 +(%)in thermochemotherapy group highly increased after four cycles treatment(P=0.016).CD3+(%)and CD4/CD8 increased and NK(%)decreased in thermochemotherapy group without statistical significance(P>0.05).In subset of adjuvant therapy,compared with chemotherapy group,CD4 +(%)in thermochemotherapy group also highly increased(P=0.022).CD3 +(%)andCD4/CD8 increased,CD8 +(%)and NK(%)decreased without statistical significance(P>0.05).In subset of first-line therapy,compared with chemotherapy group,CD3+(%)CD4+(%)and|CD4/CD8 increased,while CD8+(%)and NK(%)decreased in thermochemotherapy group without significant difference(P > 0.05).CD4+(%)had significant difference before and after treatment with different intervention methods such as hyperthermia,surgery and post-operative adjuvant therapy(P < 0.05).Thedifference of ECOG scores affected CD4+(%)before and after treatment(P < 0.05).5.In 61 cases of pancreatic cancer patients,SII and NLR decreased,while PLR did not change significantly in thermochemotherapy group.SII,NLR and PLR increased in chemotherapy group.But there was no significant difference in SII,NLR and PLR among the whole group of patients,first-line treatment patients and adjuvant treatmen patients(P > 0.05).6.Univariate survival analysis showed the mOS was related with basal NLR,sex,stage,tumor location,surgery and ECOG scores.Cox multivariate analysis showed that NLR,sex,stage and ECOG scores were independent risk factors affecting the overall survival of patients(P < 0.05).Conclusion: In advanced pancreatic cancer,combined regional hyperthermia and chemotherapy in first-line treatment could prolong PFS compared with chemotherapy alone,and OS was improved potentially.Thermochemotherapy could increase CD4 + T lymphocytes level and influence the independent prognostic factor NLR,which is probably one of the mechanisms to improve immunity and survival of pancreatic cancer patients.